A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)

Phase 1

Recruiting

• Conditions: Solid Tumors; MedDRA version: 21.0Level: LLTClassification code: 10049280Term: Solid tumour Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2024-512358-78-00
• Lead Sponsor: Merus N.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-06
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 452

Inclusion Criteria

1. Age =18 years, 10. Negative pregnancy test results available as defined by a blood human chorionic gonadotropin (hCG) test during Screening and within 7 days of Cycle 1, Day 1 in women of childbearing potential (defined as women =50 years of age or history of amenorrhea for =12 months prior to study entry); NOTE: Women with amenorrhea associated with prior treatment with antineoplastic medications are still considered as being of child-bearing potential., 11. Sexually active male and female patients of childbearing potential must agree to use one of the highly effective methods of birth control during entire study and 6 months after final administration of MCLA-128, 12. Ability to give written, informed consent prior to any study-specific Screening procedures, with the understanding that the consent may be withdrawn by the patient at any time without prejudice;, 13. Capable of understanding the mandated and optional protocol requirements, is willing and able to comply with the study protocol procedures and has signed the main informed consent document. For any optional biopsy sampling (tissue and/or blood) and long-term sample storage, additional consent is required;, 14. Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy or no satisfactory alternative treatment options are available; NOTE – Germany and Austria only: patients must have received prior standard therapy appropriate for their tumor type and stage of disease., 15. Histologic or cytologic diagnosis of locally-advanced unresectable or metastatic solid tumor malignancy with a documented NRG1 gene fusion, identified through molecular assays such as PCR, next generation sequencing-based assays [DNA or RNA], as routinely performed ast CLIA or other similarly-certified laboratories. The following tumor types are included: o Group F: NSCLC o Group G: pancreatic adenocarcinoma o Group H: any other solid tumor NOTE: Patients harboring fusions that are predicted to be non-functional, i.e.., lack of EGF-domain, will not be included in the study. For equivocal cases, including those with NRG1 as the upstream partner, the Sponsor will manually review genomic results and may request collateral testing, approve, or deny the case., 2. =1 measurable lesion, RECIST v1.1 or evaluable disease for a limited number of patients in group H, 3. ECOG 0, 1 or 2, 4. Life expectancy =12 weeks, 5. Toxicities incurred as a result of previous anti-cancer therapy resolved to =Grade 1 except for alopecia, Grade 2 sensory neurotoxicity, or any other toxicity that in the opinion of the investigator does not affect the assessment of adverse events related to the study drug, 6. Treatment with anti-cancer or investigational product within set intervals before first dose of MCLA-128: a.>14d or >5 half-lives prior to study entry, whichever is shorter. b.>14d for radiotherapy. Note: A less than 1-week wash-out period is permitted only for palliative radiation to non-CNS disease with Sponsor approval., 7. Recovery from prior surgery/other procedure/ complication to = Grade 2 or to baseline condition that in opinion of the investigator does not affect the assessment of adverse events related to the study drug., 8. Laboratory values at Screenings: a.Absolute neutrophil count =1.5 x 10^9/L without colony stimula

Exclusion Criteria

1. Pregnant or lactating;, 2. Presence of an active uncontrolled infection or an unexplained fever greater than 38.5°C during Screening up to the first scheduled day of dosing. At the discretion of the Investigator, patients with tumor fever or a clinically insignificant minor infection may be enrolled (i.e. mild upper respiratory infection);, 3. Known hypersensitivity to any of the components of MCLA-128 or history of severe hypersensitivity reactions to human or humanized monoclonal antibodies, including therapeutic antibodies;, 4. Patients with the following infectious diseases are excluded: a. known HIV b. active Hepatitis B infection (HBsAg positive) without receiving antiviral treatment Note: • Patients with active hepatitis B (HBsAg positive) must receive antiviral treatment with lamivudine, tenofovir, entecavir, or other antiviral agents, starting at least = 7 days before the initiation of the study treatment. • Patients with antecedents of Hepatitis B (anti-HBc positive, HBsAg and HBV-DNA negative) are eligible. c. positive test for Hepatitis C ribonucleic acid (HCV RNA) Note: • Patients in whom HCV infection resolved spontaneously (positive HCV antibodies without detectable HCV-RNA) or those that achieved a sustained response after antiviral treatment and show absence of detectable HCV RNA = 6 months (with the use of IFN-free regimens) or = 12 months (with the use of IFN-based regimens) after cessation of antiviral treatment are eligible; NOTE: Patients without known or suspected HIV, Hepatitis B or Hepatitis C infection do not require specific viral testing during the screening period., 5. Known symptomatic or unstable brain metastases. Patients with asymptomatic brain metastases are eligible to participate if the metastases have been radiographically and clinically stable for at least one month. If on steroids for this indication, the patient must be on a stable dose for at least one month., 6. Patients with leptomeningeal metastases, 7. Previous or concurrent malignancy (excluding non-basal cell carcinoma of skin or carcinoma in situ of the uterine cervix) unless the tumor was treated with curative or palliative intent and in the opinion of the investigator, with sponsor agreement, the previous or concurrent malignancy condition doesn't affect the assessment of safety and efficacy of the study drug;, 8. Presence of LVEF < 50% on the screening echocardiogram; or history or presence of any significant cardiovascular disease, including unstable angina or myocardial infarction within 12 months, prior to screening, congestive heart failure (NYHA Class III or IV), or ventricular arrhythmia requiring medication, 9. Presence of any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified